title: Clinical usefulness of a biomarker-based diagnostic test for acute stroke: the Biomarker Rapid Assessment in Ischemic Injury (BRAIN) study.
abstract: OBJECTIVE
  One of the significant limitations in the evaluation and management of patients with suspected acute cerebral ischemia is the absence of a widely available, rapid, and sensitive diagnostic test. The objective of the current study was to assess whether a test using a panel of biomarkers might provide useful diagnostic information in the early evaluation of stroke by differentiating patients with cerebral ischemia from other causes of acute neurological deficit.
  
  
  METHODS
  A total of 1146 patients presenting with neurological symptoms consistent with possible stroke were prospectively enrolled at 17 different sites. Timed blood samples were assayed for matrix metalloproteinase 9, brain natriuretic factor, d-dimer, and protein S100beta. A separate cohort of 343 patients was independently enrolled to validate the multiple biomarker model approach.
  
  
  RESULTS
  A diagnostic tool incorporating the values of matrix metalloproteinase 9, brain natriuretic factor, d-dimer, and S-100beta into a composite score was sensitive for acute cerebral ischemia. The multivariate model demonstrated modest discriminative capabilities with an area under the receiver operating characteristic curve of 0.76 for hemorrhagic stroke and 0.69 for all stroke (likelihood test P<0.001). When the threshold for the logistic model was set at the first quartile, this resulted in a sensitivity of 86% for detecting all stroke and a sensitivity of 94% for detecting hemorrhagic stroke. Moreover, results were reproducible in a separate cohort tested on a point-of-care platform.
  
  
  CONCLUSIONS
  These results suggest that a biomarker panel may add valuable and time-sensitive diagnostic information in the early evaluation of stroke. Such an approach is feasible on a point-of-care platform. The rapid identification of patients with suspected stroke would expand the availability of time-limited treatment strategies. Although the diagnostic accuracy of the current panel is clearly imperfect, this study demonstrates the feasibility of incorporating a biomarker based point-of-care algorithm with readily available clinical data to aid in the early evaluation and management of patients at high risk for cerebral ischemia.
authors.affiliation: Department of Medicine Neurology, Duke University Medical Center, Durham, NC 27719, USA. danl@neuro.duke.edu
authors.forename: Daniel T
authors.initials: DT
authors.lastname: Laskowitz
authors.forename: Scott E
authors.initials: SE
authors.lastname: Kasner
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Saver
authors.forename: Kerri S
authors.initials: KS
authors.lastname: Remmel
authors.forename: Edward C
authors.initials: EC
authors.lastname: Jauch
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000032:analysis / Q000097:blood; D002545:Brain Ischemia / Q000097:blood / Q000175:diagnosis* / Q000503:physiopathology; D002543:Cerebral Hemorrhage / Q000097:blood / Q000175:diagnosis / Q000503:physiopathology; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000032:analysis / Q000097:blood*; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000032:analysis / Q000097:blood*; D009414:Nerve Growth Factors / Q000032:analysis / Q000097:blood*; D011237:Predictive Value of Tests; D011446:Prospective Studies; D015203:Reproducibility of Results; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000032:analysis / Q000097:blood*; D020521:Stroke / Q000097:blood / Q000175:diagnosis* / Q000503:physiopathology; D013997:Time Factors; D055815:Young Adult
chemical_list: D015415:Biomarkers; D009414:Nerve Growth Factors; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; D020097:Natriuretic Peptide, Brain; D020780:Matrix Metalloproteinase 9